A Pilot Study of Radiation-Immune Cell Combination Therapy in Cervical Cancer

Uterine Cervical Neoplasms Clinical Trial

Official title:

A Pilot Study of Radiation-Immune Cell Combination Therapy in Recurrent or Persistent Cervical Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01194609
• Other study ID #: RadImmune Cx-1001
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: September 2, 2010
• Last updated: May 7, 2014
• Start date: September 2010
• Est. completion date: April 2012

Study information

• Verified date: May 2014
• Source: Korea Cancer Center Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Among the immune cell therapy, autologous adoptive immune cell therapy is a method to transfer the immune cells derived from peripheral white blood cells and expanded and stimulated with various cytokines and tumor specific antigens in cancer patients. Recently, the low-dose radiation is known to increase the immune response in many human cancer patients. In a clinical trial, 70% response rate with combination of low-dose radiation and adoptive immune cell therapy was reported in recurrent melanoma patients. This study is to investigate the feasibility of combination of low-dose radiation and autologous immune cell therapy in recurrent cervical cancer which is resistant to conventional palliative treatment.

Description:

Immune cell therapy is considered one of the most promising anti-cancer strategy in many human cancers. Compared to the destructive methods such as surgery, radiation, and chemotherapy, anti-cancer immune therapy is safer and less toxic method in the treatment of human cancer patients.

Among the immune cell therapy, autologous adoptive immune cell therapy is a method to transfer the immune cells derived from peripheral white blood cells and expanded and stimulated with various cytokines and tumor specific antigens in cancer patients. Recent development of the technique to expand immune cells ex vivo make autologous adoptive immune cell therapy much more feasible and popular. However, immune cell therapy showed response of below 10% currently in several clinical trials. The reason of poor response is that the adopted immune cells have to overcome the highly immune compromised environment in advanced or recurrent cancer patients.

The low-dose radiation, defined as the radiation below the therapeutic dose range, is known to increase the immune response in many human cancer patients. Despite the exact mechanism is not well known, the 'danger signal' and the decrease of T-regulatory cells by low-dose radiation are the possible mechanism of enhanced immunity by low-dose radiation. So, the combination of low-dose radiation and immune cell therapy can be a attractive strategy to recurrent or advanced cancer patients who are resistant to conventional treatment.

A challenging clinical trial performed in recurrent melanoma cancers, Dr. Rosenverg reported around 70% response rate with combination of low-dose radiation and adoptive immune cell therapy. However, the feasibility of combination of low-dose radiation and immune cell therapy is still unknown in many human cancers.

This study is to investigate the feasibility of combination of low-dose radiation and autologous immune cell therapy in recurrent cervical cancer which is resistant to conventional palliative treatment. The cervical cancer, highly responsive to radiation, becomes resistant to radiation in case of recurrent disease. We hypothetize that if the low-dose radiation can reverse the immune compromised environment, adoptive immune cells derived from the autologous peripheral blood immune cells will be highly effective in recurrent cervical cancers.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: April 2012
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Patients must have signed an approved informed consent and authorization permitting release of personal health information.

2. Age 18-75 years

3. Pathologically proven recurrent or persistent cervical cancer patients resistant to conventional palliative chemotherapy or radiation therapy

1. Persistent tumor more than 1cm after initial chemoradiation or radiation therapy

2. Persistent tumor more than 1cm after chemoradiation, radiation or chemotherapy in recurrent cervical cancer

3. Metastatic cervical cancer to lung resistant to conventional chemotherapy

4. ECOG performance status 0, 1, 2.

5. Expected survival more than 3 months

6. Patients must have adequate:

Hematologic function: ANC = 1,500/mcl, Hemoglobin >10g/dL, platelets = 100,000/mcl Renal function: creatinine = 1.5 x ULN Hepatic function: AST, ALT = 1.5 x ULN,

7. More than 3 weeks from the last day of previous chemotherapy or radiation

Exclusion Criteria:

1. Patients with immune disease or auto-immune disease (ex. rheumatoid arthritis, SLE, immune vasculitis, IDDM)

2. Immune deficiency disease

3. Cancers other than cervical cancer within 5 years

4. Acute myocardial infarction, uncontrolled hypertension

5. Severe allergic disease

6. Severe psychotic disease

7. Those who can be a candidate for curative surgery

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Uterine Cervical Neoplasms

Intervention

Biological:
• Immune cell
InnoLak two consecutive weeks every 3 weeks for 3 times

Radiation:
• Low dose radiation
20cGy whole body radiation every three weeks for three times

Locations

Country	Name	City	State
Korea, Republic of	Sang-Young Ryu	Seoul	Nowon-Gu

Sponsors (1)

Lead Sponsor	Collaborator
Korea Cancer Center Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate	Response rate according to RECIST criteria for 12 months	12months	Yes
Secondary	Toxicity	Toxcity according to CTCSEver4.0	12months	Yes